Current concepts of the mechanisms underlying solute and water reabsorption in the renal proximal tubule have been derived mostly from micropuncture of proximal convolutions on the kidney surface and in vitro microperfusion of randomly dissected proximal tubule segments. Because nephron units in the mammalian kidney are organized into superficial, mid cortical, and juxtamedullary nephrons with recognized anatomical heterogeneity the general applicablity of previous data to all proximal tubules has been questioned. Direct study of all proximal tubule segments has become possible with the technique of in vitro microperfusion. Recent studies employing this technique have documented intrinsic functional differences both between proximal tubules of superficial and juxtamedullary nephrons (internephron heterogeneity) and along the length of a given proximal tubule (intranephron heterogeneity). These findings stress the important need for studies designed to investigate further the possibility of transport heterogeneity among proximal tubule segments. The presently proposed project intends to examine transport characteristics of early, mid and late proximal tubule segments of superficial and juxtamedullary nephrons perfused in vitro. Three general types of studies are proposed. First epithelial permeability characteristics will be determined and compared. Second, the effects of luminal fluid constituents and luminal fluid flow rate will be examined. Finally studies of possible regulatory factors (peritubular protein concentration, cyclic nucleotides, prostaglandins, catecholamines) of proximal tubule reabsorption will be conducted. Such direct studies of the various proximal tubule segments are expected to determine whether functional heterogeneity plays an important role in overall proximal tubule physiology.